Anion binding by transferrins: importance of second-shell effects revealed by the crystal structure of oxalate-substituted diferric lactoferrin

Structural and spectral perturbations are seen when oxalate ion is substituted at the binding site for carbonate ion, in lactoferrin protein that belongs to the family of transferrin proteins. However, polypeptide folding and domain closure remain unaffected by the substitution. Oxalate is bound to iron at the C-lobe site of the bilobal transferrin in a symmetric 1,2-bidentate manner, whereas at the N-lobe site, the binding is asymmetric. This happens because oxalate, being a larger anion, displaces the wall forming arginine at the anion binding site.